Project Summary Healthcare-associated infections (HAIs) are a leading cause of morbidity and mortality in the United States and worldwide. The proportion of HAIs due to multidrug-resistant organisms (MDROs) has also significantly increased. Concerted efforts are needed to more clearly define the epidemiology and impact of emerging HAIs and antibiotic resistant organisms, as well as identify novel strategies to address these urgent problems. Over the past 5 years, the Centers for Disease Control and Prevention (CDC) Epicenter site at the University of Pennsylvania (Penn) and the Children's Hospital of Philadelphia (CHOP) (i.e., the Penn-CHOP Epicenter) has been engaged in numerous studies focused on HAIs and antibiotic resistance. The considerable research funding and infrastructure provided by the CDC's Prevention Epicenters Program has served to facilitate significant scientific achievements for the Penn-CHOP Epicenter. Indeed, CDC support has resulted in 38 peer-reviewed publications and 50 scientific abstracts from the Penn-CHOP Epicenter group over the past 5 years. The studies proposed in this application seek to build on this strong foundation by addressing numerous critical areas including: 1) risk factors for, and clinical impact of, emerging HAIs; 2) the role of novel diagnostic algorithms in optimizing antibiotic use; 3) the impact of innovative antimicrobial stewardship metrics and interventions; 4) emerging treatment strategies for high impact HAIs; 5) the effect of strategies focused on reducing the environmental burden of MDROs; and 6) socio-behavioral determinants of effective implementation of infection prevention and antimicrobial stewardship strategies. In these areas, the Penn- CHOP Epicenter will continue its dual focus on both adults and children. This application is comprised of a Core Project (which includes 4 primary studies) and 3 Collaborative Projects of differing scopes (i.e., small, medium, and large). These projects are: Core Project ? ?Southeastern Pennsylvania Adult and Pediatric Prevention Epicenter Network? Study #1: ?Role of Biomarkers in Antibiotic Use in the Post-Operative Setting? Study #2: ?Fecal Microbial Transplantation in Severe Clostridium difficile? Study #3: ?Development and Impact of Novel Antimicrobial Stewardship Metrics? Study #4: ?Healthcare-Associated Viral Infections in Hospitalized Children? Small Collaborative Project ? ?A Qualitative Study to Identify Meaningful Communication Strategies for Delivering Antimicrobial Stewardship Recommendations and Decisions in U.S. Hospitals? Medium Collaborative Project ? ?Reducing Vancomycin Use in the Neonatal Intensive Care Unit Large Collaborative Project ? ?Impact of Intensive Monitoring Methods for Terminal Room Cleaning on Rates of Multidrug-Resistant Organisms in the Intensive Care Unit?